JP2005514089A - Method and apparatus for testing a metered dose inhaler unit - Google Patents

Abstract

  A test apparatus and method for characterizing the aerodynamic particle size of an atomized drug released from a metered dose inhaler unit during testing with a particle characterization device. The test apparatus has a throat that is in fluid communication with the particle characterization device, a first clamp of the first jig that is detachably clamped / locked, and a canister that contains the atomizing agent. A second clamp that can be detachably clamped / locked to the delivery device of the metered dose inhaler unit that can be loaded, and the first jig can be attached to and detached from the second jig at the aligned position. And an alignment mechanism that fluidly communicates the throat with the delivery device and operatively pushes the canister, mounted on the first jig, into the delivery device of the metered dose inhaler unit, thereby atomizing And an actuating assembly having means for releasing the drug.

Description

  The present invention is generally directed to an apparatus and method for testing a metered dose inhaler unit, and more particularly, aligns the inhaler unit with a particle characterization device, controls the inhaler unit, and automatically Intended for devices and methods that are operated manually or manually.

  Pharmaceutical formulations useful for inhalation therapy to treat respiratory diseases such as asthma are often administered to patients orally or nasally in aerosolized metered doses. Such aerosolized formulations are generally provided in the form of a suspension or emulsion consisting of the pharmaceutical compound in fine powder form and a suspending medium such as a liquefied gas or propellant. The suspension is initially stored in a sealed canister that can withstand the pressure required to maintain the propellant as a liquid. A metered dose aerosolized suspension can then be dispensed from the canister when an atomized material delivery device such as a metered dose inhaler (MDI) unit is activated. Various devices for atomizing materials are well known in the pharmaceutical industry.

  Referring to FIG. 1, an example of a metered dose inhaler (MDI) unit, generally designated 5 is shown. The MDI unit 5 includes a canister generally designated 10, and the canister 10 is operably loaded within a delivery device generally designated 22. The canister 10 includes an exposed end 12, a valve end 14 opposite the exposed end 12, and an aerosol dose metering valve assembly 16 built into the valve end 14 of the canister 10. The valve assembly 16 has a spring-loaded hollow valve stem 18. Details of a typical valve assembly 16 and the interaction between the valve assembly 16 and the valve stem 18 are well understood and are not specifically shown in FIG. Typically, a suspension or solution (hereinafter the term “suspension” shall mean a suspension or solution), particularly a suspension containing a drug, is dispensed by actuating the valve assembly 16. Is done. Actuation is accomplished by moving the valve stem 18 through which a substantially reproducible fixed dose of drug 20 is delivered from the canister 10.

  In order to deliver the drug 20 to the patient with an appropriate effect, it is preferred that the canister 10 be associated with the delivery device 22. Delivery device 22 includes a housing 24 having a first open end 26, a canister cavity 28 in which canister 10 is operably loaded, and a mouthpiece 30 having a second open end 32. A nozzle assembly 34 is disposed within the housing 24 of the delivery device 22. The nozzle assembly 34 includes a valve stem receiving bore 36 in fluid communication with a nozzle orifice 38. The nozzle orifice 38 faces the second open end 32 of the mouthpiece 30.

  In order to receive a correctly metered dose of drug 20 from the canister 10, the patient loads the canister 10 from the first open end 26 of the delivery device 22 into the canister cavity 28 of the delivery device 22, and the valve assembly 16. The valve stem 18 is engaged with the valve stem receiving bore 36 of the nozzle assembly 34. With the canister 10 attached in this manner, the exposed end 12 of the canister 10 typically extends somewhat outside the housing 24 of the delivery device 22. The patient then directs the mouthpiece 30 into or into his mouth and pushes the exposed end 12 of the canister 10 with a downward force. As a result, the canister 10 moves downward relative to the valve stem 18, thereby actuating the valve assembly 16, and a fixed dose of drug 20 passes from the valve stem 18 through the nozzle orifice 38 and into the mouthpiece. It is discharged through 30 second open ends 32.

  Due to the high vapor pressure of the liquid propellant, when the suspension is pushed out of the canister 10 through the valve stem 18, the propellant vaporizes rapidly (i.e., boils) and atomizes the drug 20 moving at high speed A particle stream remains. The atomized drug 20 is guided into the patient's mouth by the mouthpiece 30 of the delivery device 22 that was previously directed to the patient's mouth or inserted into the patient's mouth. When actuated, a precisely metered atomizing agent 20 is ejected for a short time due to the design of the valve assembly 16, the design of the nozzle assembly 34, and the pressure difference between the interior of the canister 10 and the ambient atmosphere. Delivered to the patient. The patient inhales the drug 20 into his lungs simultaneously with the actuation of the valve assembly 16.

  Patients often rely on drug therapy delivered by MDI unit 5 for rapid or sustained treatment of respiratory diseases such as asthma, debilitating and potentially life-threatening. As a result, prescribed doses of aerosolized products delivered to the patient's lungs consistently meet the specifications claimed by the manufacturer and are stringent as defined by pharmaceutical regulatory authorities such as the US Food and Drug Administration (FDA) It is essential to follow the requirements. Therefore, testing the MDI unit 5 for effective and efficient drug delivery by the valve assembly 16 is an essential part of the manufacturer's quality assurance procedure.

  One aspect of testing the MDI unit 5 for effective and efficient drug delivery is released by actuating a valve assembly 16 disposed within the valve end 14 of the canister 10 containing the suspension. Measure or characterize the aerodynamic particle size of the atomized drug 20. If the aerodynamic particle size of the atomized drug 20 is too large, the drug 20 will adhere to the inner surface of the patient's throat. As a result, because the prescribed dose of respiratory medication 20 does not reach the patient's lungs, the patient cannot benefit from the therapeutic effects of medication 20 that can save lives. On the other hand, if the aerodynamic particle size of the atomized drug 20 is too small, the drug 20 will not be properly delivered to the patient's lungs. As a result, the prescribed dose of respiratory medication 20 is simply exhaled by the patient without any substantial therapeutic effect.

Particle characterization devices are often utilized to perform analytical assays on the aerodynamic particle size of atomized drug 20 released by an MDI unit, such as MDI unit 5, in determining the effect and efficiency of drug delivery. Equipment. Referring to FIG. 2, an example of a special type of particle characterization device that is particularly suitable for measuring the aerodynamic size of atomized drug 20 in a liquid aerosol is a multi-stage, generally designated 42. Particle size impactor, such as a cascade cascade impactor. Cascade impactor 42 is an 8-stage cascade impactor commercially available from Andersen Instruments, Inc. The cascade impactor 42 relies on inertial impact characterization of the aerodynamic particle size of the atomized drug 20 released by the MDI unit 5. More specifically, the cascade impactor 42 is composed of several (usually about eight) classification stages, generally represented in FIG. 2 by ST ₀ to ST ₇ . . The classification stages ST ₀ -ST ₇ are capable of classifying the aerodynamic particle size of the atomized drug 20 and the particle size typically ranges from about 9 μm to about 0.4 μm at about 28.3 lpm. As shown in FIG. 2, the cascade impactor 42 includes a zero classification stage ST ₀ , classification stages ST _{1 to} ST ₇ , a final filter 44, a base element 46, and a suction port 48. Each classification stage ST ₀ -ST ₇ includes a jet plate and a stainless steel impingement disk or filter media substrate disposed adjacent to the jet plate (not shown). The jet plate has a plurality of jet orifices through which the jet stream passes at a given speed. The collision disk has a collision surface. The final filter 44 collects all particles less than 0.4 μm. The suction port 48 allows the cascade impactor 42 to operate at a higher flow rate, thereby allowing the collection of submicron sized particles.

  Referring to FIGS. 3 and 4, a hollow throat, generally designated 58, is often used to improve or change the conditions of particulate flow into the cascade impactor 42, In this case, the throat 58 can be used to provide fluid communication between the MDI unit 5 and the cascade impactor 42 during the testing of the aerosolized formulation. The throat 58 includes a tapered end 60 and a flange neck end 62. As shown in FIG. 4, the tapered end 60 of the throat 58 is inserted into the suction port 48 of the cascade impactor 42.

During the test, the atomized particle stream to be investigated is directed through the throat 58 to the cascade impactor 42. As the atomized drug stream enters the cascade impactor 42, it becomes entrained in the jet stream flowing around the impingement disk through the jet orifice of the jet plate. In each classification stage ST _{0 to} ST ₇ , entrained atomizing agent 20 with a large aerodynamic particle size with sufficient inertia is deposited on the collision surface of the collision disk associated with a particular classification stage ST. . On the other hand, entrained particles of atomized drug 20 having a small aerodynamic particle size remain entrained in the jet stream and then on the impact surface of the impact disk present in the subsequent classification stage ST. Adhere to.

The higher the jet velocity, the more efficiently the smaller particles can be characterized. Aerodynamic particle size of the atomizing agent 20 to be collected, the collision of the classification stages ST ₀ speed of the jet stream passing through the jet orifices ~ST in _7, the collision disk jet orifice of the jet plate It depends on the distance to the surface and the collection characteristics of the preceding classification stage ST. Cascade impactor 42 is versatile in that it can classify all aerosolized formulations with extensive experimental evidence and empirical verification. Furthermore, after certain characteristics of the collected particles of atomized drug 20 have been determined, an overall aerosolized formulation can be defined by the cascade impactor 42.

  One of the problems faced when utilizing the cascade impactor 42 during characterization of the aerodynamic particle size of the atomized drug 20 released by an atomizing material delivery device such as the MDI unit 5 is the MDI unit 5 Effective and efficient fluid communication is ensured between the cascade impactor 42 and the cascade impactor 42. Therefore, it is possible to properly align the throat 58 connected to the suction port 48 of the cascade impactor 42 with the mouthpiece 30 of the delivery device 22 of the MDI unit 5 between the MDI unit 5 and the cascade impactor 42. It will help to improve communication. As a result, more accurate and reliable test results are achieved because the adhesion of the drug 20 on the inner surface of the throat 58 is reduced.

  Another problem faced during the characterization of the aerodynamic particle size of the atomized drug 20 is that the test procedure for cascade collisions essentially varies depending on the degree of human involvement or interaction normally required. . Specifically, the amount of force manually applied to the canister 10 by the patient during operation of the MDI unit 5, as well as the time for which this activation force is applied, successfully delivers a therapeutically effective dose of drug to the patient's lungs. It has been observed that whether or not it can be greatly affected. Similarly, this variability is also associated with injecting particulate streams into the cascade impactor 42 using an atomized material delivery device such as the MDI unit 5 in a test procedure performed manually by a researcher.

  The present invention is provided to address the aforementioned and other problems associated with testing microparticles such as atomized pharmaceutical formulations.

  Therefore, for the purpose of eliminating test variability due to various human analysis techniques, the present specification uses an alignment mechanism that improves the coupling between the MDI unit 5 and the cascade impactor 42, and It is proposed that the flow conditions from the unit 5 to the cascade impactor 42 can be improved. In addition, the magnitude of the normal downward force applied by the laboratory technician to the exposed end 12 of the canister 10 during quality assurance or other testing procedures, instead of the downward force applied by the patient during normal use of the MDI unit 5 We propose that it can be applied by mechanical or electromechanical means, such as some type of linear actuator that mimics force. In addition, by applying mechanical or electromechanical means, the actuation time (i.e., the time during which downward force is applied to the exposed end 12 of the canister 10) can be reproducibly controlled and can be carefully changed for assay purposes. I understood. This will be disclosed in more detail below.

  The present invention generally provides a test apparatus and method for alignment and automatic operation in characterizing the aerodynamic particle size of an atomized drug, wherein the atomized drug is delivered by metered dose inhalation. It is preferably released from the vessel (MDI) unit, guided through the hollow throat and injected into the particle size impactor.

  According to an embodiment of the present invention, the test apparatus includes a first fixture having a first clamp that is adjustable between an open position and a closed clamp position. ) And a second jig with a second clamp adjustable between an open position and a closed clamp fixing position, and the first jig can be attached to and detached from the second jig at the aligned position of the test equipment And an actuating assembly having a reciprocating member mounted on the first jig.

  The first clamp is preferably adjustable about the first hinge between an open position of the first clamp and a closed clamp fixing position.

  The first clamp preferably has a first locking mechanism. More preferably, the first locking mechanism is pivotable between a non-engaged position and an engaged position about a first pivot pin disposed within the first clamp. Further, it is preferable that the first locking mechanism has a rotatable first locking element that can be engaged with the first clamp between a loosened position and a tightened position.

  In one form of this embodiment, the first clamp removably engages the throat.

  In another form of this embodiment, the first clamp removably engages the atomizing material delivery device. The atomizing material delivery device is preferably a metered dose inhaler unit.

  The second clamp is preferably adjustable about the second hinge between an open position of the second clamp and a closed clamp fixing position.

  The second clamp preferably has a second locking mechanism. More preferably, the second locking mechanism is pivotable between a disengaged position and an engaged position about a second pivot pin disposed within the second clamp. The second locking mechanism preferably has a rotatable second locking element that can be engaged with the second clamp between the loosened position and the tightened position.

  In one form of this embodiment, the second clamp removably engages the atomizing material delivery device. According to this aspect, the atomizing material delivery device is preferably a metered dose inhaler unit.

  In another form of this embodiment, the second clamp removably engages the throat.

  The alignment mechanism preferably has an alignment post protruding from the first clamp and an alignment bore formed in the second clamp. More preferably, at the aligned position of the test device, the alignment post is inserted into the alignment bore in an engaging manner.

  In accordance with an alternative aspect of the present invention, the alignment mechanism includes an alignment post protruding from the second clamp and an alignment bore formed in the first clamp. In accordance with this aspect of the present invention, it is preferred that the alignment post is engageably inserted into the alignment bore at the aligned position of the test apparatus.

  Preferably, the throat is in fluid communication with the atomizing material delivery device when the test apparatus is in the aligned position. In the aligned position of the test apparatus, the throat is installed in the first jig at the closed clamp fixing position of the first clamp, and the atomizing material delivery device is in the second jig at the closed clamp fixing position of the second clamp. More preferably, it is installed in It is also preferred that the reciprocating member of the actuation assembly is axially aligned with the atomizing material delivery device at the aligned position of the test apparatus.

  In one embodiment, the actuation assembly has a pneumatic cylinder disposed in operative communication with the reciprocating member. In one embodiment, the actuation assembly uses a stepper motor that is in operative communication with the reciprocating member.

  Within the scope of the present invention, the actuation assembly may have an alternative mechanism, such as a solenoid, in operative communication with the reciprocating member.

  In one embodiment, the actuation assembly has an axial force measurement transducer. In one embodiment, the actuation assembly has a displacement measurement transducer for measuring acceleration. In one embodiment, the test apparatus further includes a data receiving device in electrical communication with the aforementioned transducer.

  The test device preferably includes a power source in communication with the actuation assembly. Preferably the power supply is a pneumatic source and the actuation assembly has a pneumatic cylinder. However, other actuation mechanisms are also contemplated within the scope of the present invention. Thus, in another embodiment of the invention, the power supply is an electrical energy source and the actuation assembly has a solenoid.

  The test device preferably has a control module that controls the supply of power to the actuation assembly. More preferably, the control module has a timer device that controls the time that the reciprocating member is expanded by the actuation assembly.

  In at least one embodiment of the invention, the first clamp is adapted to removably clamp engage a throat that is in fluid communication with a particle size impactor, such as a multi-stage cascade impactor. The second clamp is adapted for releasable clamping engagement with the delivery device, the delivery device having a canister cavity within which a canister containing a suspension of medicament is loaded. Has been.

  According to this embodiment, the alignment mechanism that removably couples the first jig to the second jig at the aligned position penetrates the second jig formed in the second clamp. An alignment bore that extends, and an alignment post that protrudes from the first clamp of the first jig toward the alignment bore of the second jig. When the test apparatus is in the aligned position, the alignment post of the first jig is inserted into the alignment bore of the second jig in an engaging manner. As a result, the first jig is detachably coupled to the second jig, thereby providing fluid communication between the throat and the delivery device of the MDI unit.

  The alignment mechanism of the test apparatus is between the MDI unit's delivery device (where a canister containing the atomizing drug is operably loaded into the delivery device) and the throat connected to the cascade impactor. Ensuring the existence of efficient and effective fluid communication. As a result, the test device allows for a more consistent deposition of the drug on the throat inner surface, thereby achieving more accurate, reproducible and reliable test results.

  Further, the alignment mechanism of the test apparatus ensures that when the first jig is coupled to the second jig at the aligned position of the test apparatus, the actuating assembly including the reciprocating member is securely connected to the canister. It is placed in the upper initial position so that it can be axially aligned with the canister. In general, actuation occurs when the reciprocating member of the actuation assembly pushes the canister into the canister cavity of the delivery device, thereby releasing the atomized drug.

  The actuating assembly of the test apparatus can be used in a variety of human analysis techniques by replacing the conventional source of downward force applied to the canister (i.e., the laboratory technician) with a reciprocating member, preferably an automatic pneumatic piston. Eliminate test variability due to. As a result, test equipment has typically had an aerodynamic particle size of atomized drugs that has traditionally plagued quality assurance testing procedures due to the high degree of human involvement or interaction that was previously required. Eliminates test variability during characterization.

  According to another embodiment of the invention, an apparatus is provided for aligning an atomized material delivery device, such as a metered delivery unit, with a particle characterization device. The apparatus includes an inlet conduit, a first jig removably secured to the inlet conduit, an atomizing material delivery device having an outlet conduit, a second jig removably secured to the delivery device, and a position And an alignment mechanism. The alignment mechanism interconnects the first jig and the second jig at the aligned position of the apparatus. The inlet conduit is in fluid communication with the outlet conduit at the aligned position of the device.

  The apparatus preferably has a particle characterization component with an inlet conduit. More preferably, the particle characterization component is a throat.

  The device preferably has an adapter element that interconnects the inlet and outlet conduits in the aligned position of the device.

  The alignment mechanism preferably includes a guide member supported by the first jig. The guide member is inserted into the bore of the second jig at the aligned position of the apparatus.

  The apparatus preferably has an actuation mechanism with a reciprocating member that is axially aligned with the delivery device at the aligned position of the apparatus. More preferably, the device has an actuation control module disposed in operative communication with the actuation mechanism. More preferably, the device has an axial force measurement transducer operably mounted on the actuation mechanism.

  According to this embodiment, according to the preferred and / or alternative embodiments and types described above, the first jig, the second jig, the alignment mechanism, the operating mechanism, the operation control module, and the axial force measurement transducer Is provided.

  According to another embodiment of the present invention, a test apparatus is provided that provides alignment and automatic activation during particle analysis of atomized drug released from a delivery device and directed to a particle characterization device. . The test apparatus includes a particle characterization device with an inlet conduit, a first jig, a metered dose inhaler unit, a second jig, an alignment mechanism, and an actuation assembly. The first jig has a first clamp that is detachably clamped with the inlet conduit. The metered dose inhaler unit includes a delivery device and a canister containing particles operably loaded within the delivery device. The second jig includes a second clamp that is detachably clamp-engaged with the delivery device of the metered dose inhaler unit. The alignment mechanism has an alignment post protruding from the first clamp and an alignment bore formed in the second clamp. The alignment post is adapted to be engageably inserted into the alignment bore at the aligned position of the test apparatus, thereby providing fluid communication between the inlet conduit and the delivery device of the metered dose inhaler unit. ing. The actuating assembly is mounted on the first jig and has a reciprocating member positioned in operative alignment with the canister. The reciprocating member is adapted to push the canister into the delivery device, causing the delivery device to release a metered amount of particles from the canister.

  The reciprocating member preferably has an axial force measuring transducer.

  The test apparatus preferably has a control system that controls the operation of the actuation assembly.

  According to another embodiment of the present invention, a method for testing the aerodynamic particle size of an atomized drug is provided. In the method, the first jig is engaged with the inlet portion of the particle characterization device. A canister containing the particles is operably loaded into the atomized material delivery device. A second jig is engaged with the delivery device. The aligned position of the test apparatus is achieved by removably coupling the first jig to the second jig to provide fluid communication between the inlet conduit and the delivery device. Thereafter, the release of particles from the canister is activated.

  The step of achieving the aligned position of the test apparatus involves aligning the alignment post protruding from the first jig with the alignment bore formed in the second jig, and aligning the alignment post with the alignment bore. It is preferable to include inserting into the.

  Preferably, actuating the release of particles from the canister includes causing a linearly translatable member to impinge on the canister with an axially oriented force. More preferably, the method includes the step of measuring the magnitude of the axial force applied to the canister during the actuating step.

  According to another method of the present invention, actuating the release of particles from the canister includes manually applying a force to the canister.

In accordance with yet another aspect of the invention, there are provided agents that are tested using the devices and methods disclosed herein. Such drugs include analgesics, angina preparations, anti-allergenics, anti-infectives, antihistamines, anti-inflammatory agents, antitussives, bronchodilators, adenosine 2a agonists, alpha ₄ integrin inhibitors, Selected from the group consisting of diuretics, anticholinergics, hormones, xanthines, therapeutic proteins, therapeutic peptides, vaccines, diagnostic agents, gene therapy agents, and their salts, esters, solvates, and combinations thereof Drug components.

  Accordingly, it is an object of the present invention to provide a test apparatus that allows efficient and effective fluid communication between the throat and the delivery device of the MDI unit.

  Accordingly, another object of the present invention is adapted such that the reciprocating member is positioned in operative alignment with the canister and pushes the canister into the delivery device to activate the release of a fixed dose of atomized drug. It is to provide a test device.

  While some of the objects of the present invention have been described above, other objects will become apparent when the following best described description is read in conjunction with the accompanying drawings.

  Referring now to FIG. 5, a test apparatus according to the present invention, generally designated 100, is shown. The test apparatus 100 includes a first jig, which is generally represented by 102, a second jig, which is generally represented by 104, and a first jig 102, which is generally represented by 106. 2 includes an alignment mechanism detachably coupled to the jig 104 and an actuating assembly, generally designated 108, installed on the first jig 102.

Referring generally to FIGS. 6A, 6B, and 6C, the first jig 102 according to one embodiment of the present invention is shown in detail. The first jig 102 is generally attached to the inlet structure (such as the throat 58 illustrated in FIGS. 3 and 4) of the particle characterization device (such as the cascade impactor 42 illustrated in FIGS. 2 and 4). Provides a means of attaching. Therefore, the first jig 102 has the first clamp 110. The first clamp 110 preferably has a pivot axis as defined by the first hinge 112 and a first locking mechanism, generally designated 114. The first clamp 110 is adjustable about the first hinge 112 between an open position and a closed clamp fixing position. 6A is a perspective view of the first clamp 110 of the first jig 102 in the open position installed on the throat 58. FIG. The arrow represented by C ₁ in FIG. 6A indicates the closing operation of the first clamp 110 around the first hinge 112.

FIG. 6B is a perspective view of the first clamp 110 of the first jig 102 in the closed clamp fixing position. The first locking mechanism 114 is pivotable about a first pivot pin 116 disposed in the first clamp 110 between a disengaged position and an engaged position shown in FIGS. 6A and 6B, respectively. is there. The first locking mechanism 114 preferably has a rotatable first locking element 118 mounted thereon in a threaded manner. Arrow represented by L ₁ in FIG. 6B illustrates that the first locking element 118 receives the locking operation is fixed in a state where the first locking mechanism 114 is engaged with the first clamp 110. Now, the first locking element 118 can be loosened or tightened with respect to the first clamp 110 to weaken or strengthen the locking engagement between the first clamp 110 and the throat 58, respectively. it can.

  FIG. 6C further shows a state in which the first clamp 110 of the first jig 102 is detachably clamp-engaged with the flange / neck end 62 of the throat 58. As shown in FIG. 6C, the first clamp 110 of the first jig 102 is in the closed clamp fixing position, the first clamp 110 is installed on the throat 58, and the first engagement mechanism 114 has the first engagement. The stop element 118 is in a tightened position in a locked engagement between the first clamp 110 and the throat 58.

7A, 7B, and 7C, a second jig 104 according to an embodiment of the present invention is shown. The second jig 104 generally provides a means for installing or securing an atomizing material delivery device such as the MDI unit 5 (an example of which is shown in FIG. 1). For this purpose, the second jig 104 has a second clamp 120. The second clamp 120 has a pivot axis as defined by the second hinge 122 and a second locking mechanism, generally designated 124. The second clamp 120 is adjustable around the second hinge 122 between an open position and a closed clamp fixing position. FIG. 7A is a perspective view of the second clamp 120 in the open position. The arrow represented by C ₂ in FIG. 7A indicates the closing operation of the second clamp 120 around the second hinge 122.

FIG. 7B is a perspective view of the second clamp 120 of the second jig 104 in the closed clamp fixing position. The second locking mechanism 124 is pivotable about the second pivot pin 126 disposed in the second clamp 120 between the disengaged position and the engaged position shown in FIGS. 7A and 7B, respectively. is there. The second locking mechanism 124 preferably has a rotatable second locking element 128 mounted thereon in a threaded manner. Arrows in Fig. 7B represented by L ₂ illustrates that the second locking element 128 receives the locking operation is fixed in a state where the second locking mechanism 124 is engaged with the second clamp 120. Now loosen or tighten the second locking element 128 relative to the second clamp 120 to weaken the locking engagement between the second clamp 120 and the delivery device 22 of the MDI unit 5 respectively, It can be strengthened.

  FIG. 7C further shows a state in which the second clamp 120 of the second jig 104 is detachably clamp-engaged with the delivery device 22 of the MDI unit 5. As shown in FIG.7C, the second clamp 120 of the second jig 104 is in the closed clamp fixing position, the second clamp 120 is installed in the delivery device 22, and the second locking mechanism 124 has a second The locking element 128 is in a clamped position with locking engagement between the second clamp 120 and the delivery device 22.

  Alternatively, the second clamp 120 can be configured as a draw latch with a pivoting buckle-type mechanism that engages with the delivery device 22 of the MDI unit 5. If a pull-out latch is used, a rotatable second locking element 128 is not necessary.

  Referring back to FIG. 5, the alignment mechanism 106 of the test apparatus 100 removably couples the first jig 102 to the second jig 104 at the aligned position of the test apparatus 100. The alignment mechanism 106 includes one or more alignment bores 130 and corresponding one or more alignment posts 132. In a preferred embodiment, an alignment bore 130 is formed in the second clamp 120 and extends through the second jig 104, while an alignment post 132 is the first clamp 110 of the first jig 102. Projecting toward the alignment bore 130 of the second jig 104. In an alternative embodiment, the alignment bore 130 is formed in the first clamp 110 and extends through the first jig 102 while the alignment post 130 is connected to the second clamp of the second jig 104. It is also possible to project from 120 toward the alignment bore 130 of the first jig 102.

  Referring to FIGS. 5 and 8, the test apparatus 100 is assembled by detachably coupling the first jig 102 to the second jig 104 using the alignment mechanism 106. Therefore, by inserting the alignment post 132 of the first jig 102 into the alignment bore 130 of the second jig 104 in an engaging manner, the test apparatus 100 can be brought to the aligned position. FIG. 8 shows the fully aligned position of the test apparatus 100. As shown in FIG. 8, when the test apparatus 100 is in an aligned position in this manner, the flange neck end 62 of the throat 58 (FIG. And FIG. 4) is in fluid communication with the mouthpiece 30 of the delivery device 22. The first jig 102 also attaches to the throat 58 and facilitates efficient fluid communication between the flange neck end 62 of the throat 58 and the mouthpiece 30 of the delivery device 22. You may have. The mouthpiece adapter 134 is preferably made of an elastic material so that the sealing performance at the interface with the throat 58 is improved.

  As shown in FIG. 5, the mouthpiece adapter 134 includes a flange of the throat 58 that differs from the cross-sectional area of the flow provided by the second open end 32 of the mouthpiece 30 (see, e.g., FIG. Designed to provide a substantially non-disruptive transition between the flow cross-sectional area provided by the neck end 62 (see, eg, FIG. 3). It can also be seen that the mouthpiece adapter 134 has a platform 134A that additionally supports the MDI unit 5 when the test assembly 100 is in the aligned position. However, the platform 134A is not necessary for the present invention given the support provided by the alignment post 132.

  The alignment post 132 protruding from the first clamp 110 of the first jig 102 has a round cross-sectional shape such as a circular shape, a semicircular shape, and an elliptical shape. Thus, to engageably insert the alignment post 132 into the alignment bore 130 formed in the second clamp 120 of the second jig 104, the alignment bore 130 has a rounded cross section that matches it. Should be in shape. Alternatively, the alignment post 132 can have a polygonal cross-sectional shape, such as a square, rectangle, triangle, pentagon, hexagon. In that case, the alignment bore 130 should have a matching polygonal cross-sectional shape that corresponds to the specific cross-sectional shape of the alignment post 132.

  Referring to FIG. 9A, the actuation assembly 108 is supported in a fixed orientation relative to the first fixture 102 by a mounting assembly or truss, generally designated 136. The truss 136 includes a support base 138 attached to the first clamp 110 of the first jig 102, an arm 140 supported by the support base 138, and a platform 142 that couples the actuation assembly 108 to the arm 140. . Actuating assembly 108 includes a linear reciprocating member 144, such as a plunger or rod, and an axial force measuring transducer 148, such as a load cell, disposed in a proximal relationship with the distal end or head 146 of linear reciprocating member 144. Have. Alternatively, the reciprocating member 144 may comprise a rotary actuator with a linear reciprocating member such as an arm.

  Actuation assembly 108 can be any device adapted to convert an input amount of supplied power into an axial displacement of reciprocating member 144 due to force. Furthermore, it should be understood that in other embodiments, it can be manually activated if necessary. As an example, the actuation assembly 108 can comprise a pneumatic cylinder, a hydraulic cylinder, a linear motor and gear assembly, or a solenoid. For non-pneumatic methods of operation, such as the use of a motor and gear assembly, the converter 148 can be configured by measuring the current drawn into the motor and choosing a method to correlate such measurements with force measurements. Can be eliminated. Currently, it is preferred that the actuation assembly 108 includes a pneumatic cylinder, in which case the reciprocating member 144 includes a piston, as will be appreciated by those skilled in the art. The actuating assembly 108 expands or translates the reciprocating member 144 in the axial direction to hold down the canister 10 of the delivery device 22 and thereby automatically actuates the MDI unit 5. This will be described in more detail below. As shown in FIGS. 8 and 9A, the truss 136 ensures that the reciprocating member 144 ensures that the canister 10, valve stem 18, and nozzle assembly 34 when the test apparatus 100 is in the aligned position. And axial alignment. Furthermore, this arrangement ensures that the actuating assembly 108 operates correctly, and as a result, the MDI unit 5 operates correctly. Actuating assembly 108 is preferably a double-acting type that requires power to be extended or retracted to retract and retract, and can control all motion of reciprocating member 144. Alternatively, a single-acting actuating unit can be provided that utilizes a spring to retract the reciprocating member 144 after power is applied.

  In an alternative embodiment, the actuation assembly 108 can be mounted on the second jig 104 instead of the first jig 102. In other alternative embodiments, the actuating assembly 108 is not installed in the first jig 102 or the second jig 104, but instead the reciprocating member 144 of the actuating assembly 108 is axially aligned with the canister 10. The actuating assembly 108 can then be mounted to a fixation member or skeleton in such a way that it can be suitably placed directly above the canister 10.

  The operation of the actuation assembly 108 will now be described with reference to FIGS. 9A-9C. In general, actuation occurs when the reciprocating member 144 of the actuation assembly 108 pushes the canister 10 into the canister cavity 28 of the delivery device 22. More specifically, before the start of the operation stroke, as shown in FIG. 9A, the reciprocating member 144 is disposed at a retracted position above the canister 10. When the actuation stroke is started, the reciprocating member 144 is pushed in a downward direction toward the exposed end 12 of the canister 10 as indicated by an arrow in FIG. 9B. As also shown in FIG. 9B, the reciprocating member 144 continues in the downward direction during the actuation stroke and contacts the exposed end 12 of the canister 10. After contact, actuation occurs and the reciprocating member 144 pushes the canister 10 into the canister cavity 28 of the delivery device 22 with a downward force, as shown in FIG. 9C. Actuation occurs by moving the valve stem 18 of the valve assembly 16, thereby releasing a fixed dose of atomized drug 20 from the canister 10, through the mouthpiece 30, through the throat 58, and the cascade impactor. 42 (see Fig. 4). Referring back to FIG. 9A, after actuation, the reciprocating member 144 is pushed upward and returns to the retracted initial position above the canister 10.

  Referring now to FIG. 10, a control unit or control system, generally designated 150, for interfacing with the test apparatus 100 is provided. The control system 150 preferably serves to control the operation of the actuation assembly 108, including expansion of the reciprocating member 144 of the actuation assembly 108 and subsequent retraction. More specifically, the control system 150 allows the operator to initiate an expansion / retraction sequence, and in addition, during the expansion and retraction strokes, the amount of power supplied to the actuation assembly 108, during the expansion and retraction strokes Preferably, each flow rate of power supplied to the actuation assembly 108 as well as the duration of actuation (ie, the time during which the reciprocating member 144 is expanded) can be controlled. These control parameters have been observed to affect the performance of metered delivery devices such as MDI unit 5, as well as the hydrodynamic and other properties of the particulate stream exiting the device. The control system 150 receives, regulates, stores, processes and / or displays signals generated / transmitted by the axial force measurement transducer 148 of the actuation assembly 108 during operation of the MDI unit 5 It is further preferable to provide a means such as an electronic device.

  Accordingly, FIG. 10 schematically illustrates an example of a suitable control system 150 that can be provided when the actuation assembly 108 has a double-acting pneumatic cylinder and fluid such as air is used as the power medium. The control system 150 generally comprises a control module 152 and an electronic circuit or device 190. A power supply source 154 such as an air compressor or a tank containing pressurized air supplies pressurized air to the control module 152 through an air supply line 156. A power switch 158 is provided that controls power supply from the power supply 160 to any component of the control system 150 that requires power for operation.

  In order to control the flow of pressurized air to the actuation assembly 108, a solenoid activated air valve or manifold assembly 162 is provided. In the preferred embodiment of the double-acting actuation assembly 108, two air lines 164 and 166 are implemented by the reciprocating member 144, fluidly interconnecting the air valve assembly 162 and the actuation assembly 108, respectively. Provide sufficient amount of aerodynamic power to initiate each expansion and retraction stroke. The air valve assembly 162 is activated by operation of a start button 168 that initiates the expansion and retraction sequence. This sequence is controlled by the timer relay unit 170. The operator can use the timer relay unit 170 to set the time that pneumatic power is supplied through the air line 164 to activate the expansion stroke of the reciprocating member 144. When this preset time expires, the timer relay unit 170 communicates with the air valve assembly 162 to provide air power through the air line 166 and retract the reciprocating member 144.

  The control system 150 also includes a flow regulator to control the flow rate of each air supplied through the air lines 164 and 166. The operator can adjust these flow rates using flow rate adjustment knobs 172 and 174, respectively. In addition, a pressure regulator is provided to control the fluid pressure of each air stream supplied through the air lines 164 and 166. The operator can adjust these fluid pressures using pressure adjustment knobs 182 and 184, respectively. Pressure gauges 186 and 188 indicating pressure levels in the air lines 164 and 166 are provided, respectively. If necessary, additional fluid conduits and / or components (particularly diagrammatically) within the control module 152 to provide a complete pneumatic circuit that allows the various components of the control system 150 to operate successfully and communicate with related components. Those skilled in the art will appreciate that a not shown) is provided.

  As described above, the control system 150 further includes an electronic circuit or electronic device 190. Electronic circuit or device 190 communicates with axial force measurement transducer 148 of actuation assembly 108 through electrical cable 192. Electronic device 190 serves to receive one or more signals generated by transducer 148 that are proportional to the amount of axial force applied to canister 10 by actuation assembly 108. Also, the electronic device 190 includes one or more read components received from the transducer 148, a read component that displays the force applied by the actuation assembly 108 for human reading, as schematically depicted in FIG. It can include memory components that store signals, printer components that provide archival copies of data, and signal conditioning circuitry such as A / D converters and amplifiers. Thus, as will be appreciated by those skilled in the art, the electronic device 190 can be an IC chip, memory register, display device, computer terminal, PC unit, and equivalents of such components, other related I / O peripheral devices. Or a combination of two or more of such components. The electronic device 190 is remotely located with respect to the control module 152 or integrated with the control module 152. The electrical line 194 shown in FIG. 10 represents a power supply line and / or a data communication line to the electronic device 190.

  Thus, it can be seen that the control system 150 can be used to test the MDI unit 5 by changing the axial force applied to the canister 10 during operation and the time to apply this axial force. While one or more tests are being performed, the force data obtained from the transducer 148 as well as the operating time set by the operator are correlated with the particle characterization data obtained from the cascade impactor 42. Can be compared. In this way, the optimum operating condition of the MDI unit 5 can be investigated. Therefore, the test results obtained using the test apparatus 100 and the cascade impactor 42 together can be used to improve the design of a drug delivery device such as the MDI unit 5 and to vary the variety of materials delivered by such a device. Composition and formulation can be evaluated and the instructions for such devices provided to the patient can be modified.

  It is also within the scope of the present invention to utilize the alignment provided by alignment mechanism 106 and mounting assembly 136 to improve the procedure for manually operating MDI unit 5. That is, the present invention provides reproducible data by using alignment mechanism 106 and mounting assembly 136 to maintain perfect alignment without the automation provided by actuation assembly 108 and control system 150. Are obtained.

FIG. 11 shows another embodiment of an assembled test device according to the present invention. This embodiment is similar to the embodiment depicted in FIG. However, in the embodiment of FIG. 11, as shown in the figure, the alignment post 132 can be positioned at various angles (indicated by letters a and b) with respect to a horizontal reference line represented by `` l ''. it can. More specifically, the alignment posts 132 can be arranged at various locations above and below the horizontal line l indicated by arrows in FIG. Without being bound by any particular theory, when the alignment post is positioned at these locations, it can better mimic how the smoke spray coming out of the canister is targeting the patient's throat. As a result, more consistent test results can be obtained. As a result, the positioning of the alignment bore 130 can be adjusted as deemed appropriate. The alignment bore 132 can be positioned at various angles along a vertical reference line (denoted by l ₁ ) orthogonal to the horizontal reference line l, but the bore 132 deviates from the vertical line l ₁ It should be understood that such movements can also be shown.

  FIG. 12 shows a perspective view of an assembled test device according to the present invention. As shown in the figure, the alignment bore 132 is positioned at an angle below the horizontal reference line l. A similar configuration is shown in the cross-sectional view of the device described in FIG.

  Examples of drugs that can be tested using the test apparatus 100 and method according to the present invention include, but are not limited to, analgesics (eg, codeine, dihydromorphine, ergotamine, fentanyl, morphine), angina preparations (E.g. diltiazem), antiallergic substances (e.g. cromoglycate (e.g. as sodium salt), ketotifen, nedocromil (e.g. as sodium salt)), anti-infectives (e.g. cephalosporin, penicillin, streptomycin, sulfonamides , Tetracycline, pentamidine), antihistamines (e.g. metapyrylene), anti-inflammatory agents (e.g. beclomethasone (e.g. as dipropionate), budesonide, ciclesonide, fluticasone (e.g. as propionate), flunisolide, mometasone (e.g. (As carboxylic acid esters), rofleponide, tipredane, triamcinolone (e.g. as acetonide), 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androst-1,4- Diene-17β-carbothioic acid S- (2-oxo-tetrahydro-furan-3-yl) ester), antitussives (e.g. noscapine), bronchodilators (e.g. salbutamol, salmeterol (e.g. as salmeterol xinafoate), ephedrine, Adrenaline, fenoterol (e.g. as fenoterol hydrobromide), formoterol (e.g. as formoterol fumarate), isoprenaline, metaproterenol, phenylephrine, pyrbuterol (e.g. as pyrbuterol acetate), phenylpropanolamine, leproterol (e.g. leproterol hydrochloride) (As roll), limiterol, terbutaline (e.g. as terbutaline sulfate), isoetarine, tulbuterol, orciprenaline, (-)-4-amino-3,5-dichloro-α-[[[6- [2- (2-pyridinyl) ethoxy ] Hexyl] amino] methyl] benzenemethanol, albuterol (eg as free base or sulfate), 4-hydroxy-7- [2-[[2-[[3- (2-phenylethoxy) propyl] sulfonyl] ethyl] Amino] ethyl-2 (3H) -benzothiazolone), adenosine 2a agonist (e.g. (2R, 3R, 4S, 5R) -2- [6-amino-2- (1S-hydroxymethyl-2-phenyl) -Ethylamino) -purin-9-yl] -5- (2-ethyl-2H-tetrazol-5-yl) -tetrahydro-furan-3,4-dione (eg as maleate)), α4 integrin inhibition Substances (e.g. (2S) -3- [4-({[4- (aminocarbonyl) -1-piperidinyl] carbonyl} oxy) pheny ] -2-[((2S) -4-methyl-2-{[2- (2-methylphenoxy) acetyl] amino} pentanoyl) amino] propanoic acid (eg as free acid or potassium salt)]), diuretic (E.g. amiloride), anticholinergics (e.g. ipratropium (e.g. as ipratropium bromide), tiotropium, atropine, oxitropium), hormones (e.g. cortisone, hydrocortisone, prednisolone), xanthines (e.g. aminophylline, corintheo Filinates, lysine theophyllates, theophylline), therapeutic proteins and peptides (eg, insulin, glucagon), and vaccines, diagnostic agents, and gene therapy agents.

  In order to optimize the activity / stability of the drug and / or to minimize the solubility of the drug in the propellant liquid, the drug may be in salt form (e.g., alkali metal salt or It will be apparent to those skilled in the art that it can be used as an amine salt or as an acid addition salt), in the form of an ester (e.g., as a lower alkyl ester), or in the form of a solvate (e.g., as a hydrate). .

  Preferred agents are selected from albuterol, salmeterol, fluticasone propionate, ipratropium, and beclomethasone dipropionate, and salts or solvates thereof such as albuterol sulfate, salmeterol xinafoate, and ipratropium bromide.

  Drug combinations can also be delivered. Preferred formulations containing a combination of active ingredients are salbutamol (e.g. free base or sulfate) in combination with an anti-inflammatory steroid such as beclomethasone ester (e.g. dipropionate), fluticasone ester (e.g. propionate), budesonide, etc. Salt), salmeterol (eg, as xinafoate), or formoterol (eg, as fumarate). A particularly preferred combination is a combination of fluticasone propionate and salmeterol or a salt thereof (particularly xinafoate). Another combination of particular interest is the combination of budesonide and formoterol (eg as fumarate).

  Suitable propellants for oral inhalation by a patient, suitable for use as a suspending medium in a sealed canister such as canister 10, include, but are not limited to, dichlorodifluoromethane, tetrachlorofluoroethane, 1 1,1,1,2-tetrafluoroethane (commonly known as `` propellant 134a '' or `` P134a ''), 1,1,1,2,3,3,3-heptafluoropropane (commonly referred to as `` propellant 227 '' Or low-boiling fluorocarbons such as “P227”).

  It will be understood that various details of the invention may be changed without departing from the scope of the invention. Moreover, the foregoing description is not intended to be limiting, but merely illustrative and the present invention is defined by the following claims.

1 is a vertical cross-sectional view of a known metered dose inhaler (MDI) unit in operation with a canister operably loaded in a delivery device. 1 is a perspective view of a known multistage cascade impactor. FIG. FIG. 3 is a perspective view of a known throat adapted for use with the cascade impactor shown in FIG. FIG. 4 is a perspective view of the throat of FIG. 3 coupled to the cascade impactor of FIG. 1 is a perspective view of a test apparatus provided by the present invention. 6A is a perspective view of the first clamp of the first jig provided with the test apparatus of FIG. 5, and shows the first clamp in an open position when installed on the throat of FIG. . 6B is a perspective view of the first clamp of the first jig in a closed position in which the throat of FIG. 3 is detachably engaged. FIG. 6C is a side view of the first clamp of the first jig, showing the first hinge. FIG. 7A is a perspective view of the second clamp of the second jig provided with the test apparatus of FIG. 5, and is opened when the second clamp is installed on the delivery device of the MDI unit shown in FIG. It is a figure shown by a position. FIG. 7B is a perspective view of the second clamp of the second jig in the closed position removably engaged with the delivery device of the MDI unit shown in FIG. FIG. 7C is a side view of the second clamp of the second jig, and shows the second hinge. FIG. 6 is a perspective view of the assembled test apparatus of FIG. 5 in an aligned position in accordance with the present invention. FIG. 9A is a vertical cross-sectional view of the test apparatus during operation when the actuator is moved from a retracted position to a fully expanded position or a fully expanded position. FIG. 9B is a vertical cross-sectional view of the test apparatus during operation when the actuator is moved from a retracted position to a fully expanded position or a fully expanded position. FIG. 9C is a vertical cross-sectional view of the test apparatus during operation when the actuator is moving from a retracted position to a fully expanded position or a fully expanded position. FIG. 10 is a schematic diagram of a control unit in operable communication with the test apparatus shown in FIGS. FIG. 6 is a perspective view of the assembled test apparatus of FIG. 5 according to the present invention. 1 is a perspective view of an assembled test device according to the present invention. FIG. 1 is a cross-sectional view of an assembled test device according to the present invention. FIG.

Claims (59)

A test apparatus for an atomized material delivery device comprising:
(a) a first jig having a first clamp adjustable between an open position and a closed clamp fixing position;
(b) a second jig having a second clamp adjustable between an open position and a closed clamp fixing position;
(c) an alignment mechanism that removably couples the first jig to the second jig at an aligned position of the test apparatus;
(d) A test apparatus comprising: an actuating assembly including a reciprocating member mounted on the first jig.   The test apparatus according to claim 1, wherein the first clamp is adjustable between an open position of the first clamp and a closed clamp fixing position around the first hinge.   2. The test apparatus according to claim 1, wherein the first clamp has a first locking mechanism.   4. The test apparatus of claim 3, wherein the first locking mechanism is pivotable between a non-engaged position and an engaged position about a first pivot pin disposed in the first clamp. .   4. The test apparatus according to claim 3, wherein the first locking mechanism includes a rotatable first locking element that can be engaged with the first clamp between a loosened position and a tightened position.   2. The test apparatus according to claim 1, wherein the first clamp is detachably engaged with the throat.   The test apparatus of claim 1, wherein the first clamp is removably engaged with an atomizing material delivery device.   8. The test apparatus of claim 7, wherein the atomized material delivery device is a metered dose inhaler unit.   The test apparatus of claim 1, wherein the second clamp is adjustable between a second clamp open position and a closed clamp fixing position about a second hinge.   2. The test apparatus according to claim 1, wherein the second clamp has a second locking mechanism.   11. The test apparatus of claim 10, wherein the second locking mechanism is pivotable between a disengaged position and an engaged position about a second pivot pin disposed within the second clamp. .   11. The test apparatus of claim 10, wherein the second locking mechanism has a rotatable second locking element that can engage the second clamp between a relaxed position and a tightened position.   The test apparatus of claim 1, wherein the second clamp is removably engaged with an atomizing material delivery device.   14. The test apparatus of claim 13, wherein the atomized material delivery device is a metered dose inhaler unit.   2. The test apparatus according to claim 1, wherein the second clamp is detachably engaged with the throat.   2. The test apparatus according to claim 1, wherein the alignment mechanism includes an alignment post protruding from the first clamp and an alignment bore formed in the second clamp.   17. The test apparatus of claim 16, wherein the alignment post is engageably inserted into the alignment bore at a position where the test apparatus is aligned with respect to a horizontal line.   18. The test apparatus of claim 17, wherein the alignment post is engagably inserted into the alignment bore on a horizontal line.   18. The test apparatus of claim 17, wherein the alignment post is engagably inserted into the alignment bore at an angle with respect to a horizontal line.   2. The test apparatus according to claim 1, wherein the alignment mechanism includes an alignment post protruding from the second clamp and an alignment bore formed in the first clamp.   21. The test apparatus of claim 20, wherein the alignment post is engageably inserted into the alignment bore at a position where the test apparatus is aligned with a horizontal line.   24. The test apparatus of claim 21, wherein the alignment post is engagably inserted into the alignment bore on a horizontal line.   24. The test apparatus of claim 21, wherein the alignment post is engagably inserted into the alignment bore at an angle with respect to a horizontal line.   The test apparatus of claim 1, wherein the throat is in fluid communication with an atomizing material delivery device at an aligned position of the test apparatus.   The throat is installed on the first jig at the closed clamp fixing position of the first clamp, and the atomizing material delivery device is installed on the second jig at the closed clamp fixing position of the second clamp. 25. The test device of claim 24, wherein:   25. The test apparatus of claim 24, wherein the reciprocating member of the actuation assembly is axially aligned with the atomizing material delivery device.   The test apparatus of claim 1, wherein the actuation assembly includes a pneumatic cylinder disposed in operative communication with the reciprocating member.   The test apparatus of claim 1, wherein the actuation assembly includes a stepper motor disposed in operative communication with the reciprocating member.   The test apparatus of claim 1, wherein the actuation assembly comprises a solenoid in operative communication with the reciprocating member.   The test apparatus of claim 1, wherein the actuation assembly comprises an axial force measurement transducer.   32. The test apparatus of claim 30, comprising a data receiving device in electrical communication with the axial force measurement transducer.   The test apparatus of claim 1, wherein the actuation assembly comprises a displacement measurement transducer.   The test apparatus of claim 1, comprising a power supply in communication with the actuation assembly.   34. The test apparatus of claim 33, wherein the power supply source is a pneumatic source and the actuation assembly comprises a pneumatic cylinder.   34. The test apparatus of claim 33, wherein the power supply is an electrical energy source and the actuation assembly has a solenoid.   The test apparatus of claim 1, comprising a control module that controls the supply of power to the actuation assembly.   37. The test apparatus of claim 36, wherein the control module comprises a timer device that controls the time that the reciprocating member is expanded by the actuation assembly. A drug to be tested using the device of claim 1, comprising an analgesic, an angina preparation, an antiallergic agent, an antiinfective, an antihistamine, an antiinflammatory agent, an antitussive, a bronchodilator, adenosine 2a Agonists, alpha ₄ integrin inhibitors, diuretics, anticholinergics, hormones, xanthines, therapeutic proteins, therapeutic peptides, vaccines, diagnostic agents, gene therapy agents, and their salts, esters, solvates, and A medicament comprising a drug component selected from the group consisting of these combinations. An apparatus for aligning an atomizing material delivery device, such as a metered delivery unit, with a particle characterization device comprising:
(a) an inlet conduit;
(b) a first jig detachably fixed to the inlet conduit;
(c) an atomizing material delivery device having an outlet conduit;
(d) a second jig detachably fixed to the delivery device;
(e) an alignment mechanism that interconnects the first jig and the second jig at the aligned position of the device, wherein the inlet conduit is at the outlet at the aligned position of the device A device in fluid communication with a conduit.   40. The apparatus of claim 39, comprising a particle characterization component comprising the inlet conduit.   41. The apparatus of claim 40, wherein the particle characterization component is a throat.   40. The device of claim 39, comprising an adapter element that interconnects the inlet conduit and the outlet conduit in the aligned position of the device.   The alignment mechanism has a guide member supported by the first jig, and the guide member is inserted into the bore of the second jig at the aligned position of the apparatus. The device described in 1.   40. The apparatus of claim 39, comprising an actuation mechanism comprising a reciprocating member that is axially aligned with the delivery device at an aligned position of the apparatus.   45. The apparatus of claim 44, comprising an actuation control module disposed in operative communication with the actuation mechanism.   45. The apparatus of claim 44, comprising an axial force measurement transducer operably mounted on the actuation mechanism.   40. The apparatus of claim 39, wherein the actuation mechanism comprises a stepper motor. A drug to be tested using the device of claim 39, comprising an analgesic, an angina preparation, an antiallergic agent, an antiinfective, an antihistamine, an antiinflammatory agent, an antitussive, a bronchodilator, adenosine 2a Agonists, alpha ₄ integrin inhibitors, diuretics, anticholinergics, hormones, xanthines, therapeutic proteins, therapeutic peptides, vaccines, diagnostic agents, gene therapy agents, and their salts, esters, solvates, and A medicament comprising a drug component selected from the group consisting of these combinations. A test apparatus that provides alignment and automatic activation during particle analysis of atomized drug released from a delivery device and directed to a particle characterization device,
(a) a particle characterization device with an inlet conduit;
(b) a first jig having a first clamp that is detachably clamped with the inlet conduit;
(c) a metered dose inhaler unit comprising a delivery device and a canister containing particles operably loaded in the delivery device;
(d) a second jig comprising a second clamp that is detachably clamp-engaged with the delivery device of the metered dose inhaler unit;
(e) an alignment mechanism comprising an alignment post projecting from the first clamp and an alignment bore formed in the second clamp, wherein the alignment post is configured such that the test device is relative to a horizontal line. Alignment adapted to be engagedly inserted into the alignment bore in an aligned position thereby providing fluid communication between the inlet conduit and the delivery device of the metered dose inhaler unit Mechanism,
(f) an actuating assembly comprising a reciprocating member mounted on the first jig and positioned in operative alignment with the canister, wherein the reciprocating member removes the canister from the delivery device; An actuation assembly adapted to be pushed into the delivery device to release a fixed dose of particles from the canister;
Test equipment with   50. The test apparatus of claim 49, wherein the alignment post is engagably inserted into the alignment bore on a horizontal line.   50. The test apparatus of claim 49, wherein the alignment post is engagably inserted into the alignment bore at an angle with respect to a horizontal line.   50. The test apparatus of claim 49, wherein the reciprocating member comprises an axial force measurement transducer.   50. The test apparatus of claim 49, comprising a control system that controls operation of the actuation assembly. An agent to be tested using the device of claim 49, comprising an analgesic, an angina preparation, an antiallergic agent, an anti-infective agent, an antihistamine, an anti-inflammatory agent, an antitussive agent, a bronchodilator, adenosine 2a Agonists, alpha ₄ integrin inhibitors, diuretics, anticholinergics, hormones, xanthines, therapeutic proteins, therapeutic peptides, vaccines, diagnostic agents, gene therapy agents, and their salts, esters, solvates, and A medicament comprising a drug component selected from the group consisting of these combinations. A method for testing the aerodynamic particle size of an atomized drug, comprising:
(a) engaging the first jig with the inlet portion of the particle characterization device;
(b) operably loading a canister containing particles into an atomizing material delivery device;
(c) engaging a second jig with the delivery device;
(d) achieving an aligned position of the test apparatus by removably coupling the first jig to the second jig to provide fluid communication between an inlet conduit and the delivery device; And steps to
(e) activating the release of particles from the canister.   The step of achieving the aligned position of the test apparatus aligns an alignment post protruding from the first jig with an alignment bore formed in the second jig, and the alignment post 56. The method of claim 55, comprising inserting a into the alignment bore.   56. The method of claim 55, wherein actuating the release of particles from the canister comprises manually applying a force to the canister.   56. The method of claim 55, wherein actuating the release of particles from the canister comprises causing a linearly translatable member to impact the canister with an axially oriented force.   59. The method of claim 58, comprising measuring the magnitude of the axial force applied to the canister during the actuating step.

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